期刊
SCIENCE ADVANCES
卷 7, 期 1, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abd6889
关键词
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资金
- National Institutes of Health [HL095722]
- Fundacao para a Ciencia e a Tecnologia through MIT-Portugal [TB/ECE/0013/2013]
- Football Players Health Study at Harvard
- National Football League Players Association
This study introduces a nanoparticle platform for BBB-independent delivery of siRNA in TBI, achieved through modulation of nanoparticle surface chemistry and coating density. The engineered nanoparticles showed higher brain accumulation and gene silencing compared to nonengineered nanoparticles, suggesting a promising drug delivery approach for TBI treatment.
Small interfering RNA (siRNA)-based therapeutics can mitigate the long-term sequelae of traumatic brain injury (TBI) but suffer from poor permeability across the blood-brain barrier (BBB). One approach to overcoming this challenge involves treatment administration while BBB is transiently breached after injury. However, it offers a limited window for therapeutic intervention and is applicable to only a subset of injuries with substantially breached BBB. We report a nanoparticle platform for BBB pathophysiology-independent delivery of siRNA in TBI. We achieved this by combined modulation of surface chemistry and coating density on nanoparticles, which maximized their active transport across BBB. Engineered nanoparticles injected within or outside the window of breached BBB in TBI mice showed threefold higher brain accumulation compared to nonengineered PEGylated nanoparticles and 50% gene silencing. Together, our data suggest that this nanoparticle platform is a promising next-generation drug delivery approach for the treatment of TBI.
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